Rapid decrease of circulating tumor DNA predicted the treatment effect of nivolumab in a lung cancer patient within only 5 days

Abstract

A 77-year-old Japanese man presented to our hospital with a 1-month history of low back pain and was diagnosed as having stage IV EGFR mutation-positive lung adenocarcinoma. After treatment with EGFR tyrosine kinase inhibitor and cytotoxic chemotherapy, nivolumab was started as fourth-line therapy. Remarkable regression of the primary tumor was observed, suggesting high anti-tumor activity of nivolumab. We retrospectively investigated the change in circulating tumor DNA (ctDNA) variant allele fractions in serial plasma samples before and after the nivolumab therapy. Targeted sequencing analysis showed tumor-derived TP53R249S and EGFRL858R mutations detectable in plasma, and the timing of decrease was only 5 days, much earlier than the appearance of radiological changes. Overall, these results suggest that ctDNA might reflect tumor burden and might be a surrogate marker of the therapeutic efficacy of immune checkpoint therapy.

Biomarkers for predicting efficacy of PD-1/PD-L1 inhibitors

“…It was observed that circulating tumor DNA (ctDNA) in responding patient decreased quickly in 5 days after first nivolumab administration. The phenomenon is meaningful that the shift in ctDNA is prior to second administration and radiological change [ 99 ]. Compared with detectable abundance at baseline, undetectable ctDNA after therapy beginning indicates robust anti-tumor effect which is valuable for early patient selection [ 98 , 100 ].…”